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凋亡细胞的稳定:僵尸细胞的产生。

Stabilization of apoptotic cells: generation of zombie cells.

作者信息

Oropesa-Ávila M, Andrade-Talavera Y, Garrido-Maraver J, Cordero M D, de la Mata M, Cotán D, Paz M V, Pavón A D, Alcocer-Gómez E, de Lavera I, Lema R, Zaderenko A P, Rodríguez-Moreno A, Sánchez-Alcázar J A

机构信息

Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), and Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Sevilla, Spain.

Laboratorio de Neurociencia Celular y Plasticidad, Universidad Pablo de Olavide, Sevilla, Spain.

出版信息

Cell Death Dis. 2014 Aug 14;5(8):e1369. doi: 10.1038/cddis.2014.332.

DOI:10.1038/cddis.2014.332
PMID:25118929
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4454307/
Abstract

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn(2+) (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.

摘要

细胞凋亡的特征是细胞成分降解,但质膜保持完整。凋亡微管网络(AMN)在细胞凋亡过程中形成,在质膜下方形成一种皮质结构,维持质膜完整性。凋亡细胞的另一个特征是产生高活性氧(ROS),这可能对细胞有潜在危害。本研究的目的是开发一种方法,用于稳定凋亡细胞以用于诊断和治疗应用。通过使用由紫杉醇(一种微管稳定剂)、Zn(2+)(一种半胱天冬酶抑制剂)和辅酶Q10(一种脂质抗氧化剂)组成的混合物,我们能够在细胞培养物中稳定H460凋亡细胞至少72小时,防止继发性坏死。稳定的凋亡细胞保持许多凋亡细胞特征,如凋亡微管的存在、质膜完整性、低细胞内钙水平和线粒体极化。凋亡细胞的稳定可能为细胞凋亡检测和治疗开辟新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/ce03f863bf13/cddis2014332f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/914d4d9fa150/cddis2014332f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/040479042d1f/cddis2014332f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/d19f6b14706a/cddis2014332f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/2b1b27a57f2f/cddis2014332f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/f01f13ee4f74/cddis2014332f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/ce03f863bf13/cddis2014332f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/914d4d9fa150/cddis2014332f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/040479042d1f/cddis2014332f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/d19f6b14706a/cddis2014332f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/2b1b27a57f2f/cddis2014332f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/f01f13ee4f74/cddis2014332f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fd/4454307/ce03f863bf13/cddis2014332f6.jpg

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本文引用的文献

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Prospects of apoptotic cell-based therapies for transplantation and inflammatory diseases.基于细胞凋亡的移植和炎症性疾病治疗的前景。
Immunotherapy. 2013 Oct;5(10):1055-73. doi: 10.2217/imt.13.103.
2
Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis.在细胞凋亡的执行阶段,凋亡微管在细胞皮层的无活性胱天蛋白酶区域划定界限。
Cell Death Dis. 2013 Mar 7;4(3):e527. doi: 10.1038/cddis.2013.58.
3
Mechanism of zinc-mediated inhibition of caspase-9.锌介导的 caspase-9 抑制机制。
线粒体和半胱天冬酶途径参与了nardosinen在MCF-7乳腺癌细胞系中诱导凋亡的过程。
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A microfluidic platform for modeling metastatic cancer cell matrix invasion.用于模拟转移性癌细胞基质侵袭的微流控平台。
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Lipopolysaccharide and its threatening zombie-like nature: unlive, harmful and tough (but not impossible) to eliminate.脂多糖及其类似僵尸的威胁性本质:无生命、有害且难以消除(但并非不可能)。
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Inhibition by zinc of deoxycholate-induced apoptosis in HCT-116 cells.锌对脱氧胆酸钠诱导的 HCT-116 细胞凋亡的抑制作用。
J Cell Biochem. 2012 Feb;113(2):650-7. doi: 10.1002/jcb.23394.
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Apoptotic microtubule network organization and maintenance depend on high cellular ATP levels and energized mitochondria.凋亡微管网络的组织和维持依赖于高细胞 ATP 水平和能量充足的线粒体。
Apoptosis. 2011 Apr;16(4):404-24. doi: 10.1007/s10495-011-0577-1.
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The antioxidant role of coenzyme Q.辅酶Q的抗氧化作用。
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The apoptotic microtubule network preserves plasma membrane integrity during the execution phase of apoptosis.凋亡微管网络在凋亡执行阶段维持质膜完整性。
Apoptosis. 2007 Jul;12(7):1195-208. doi: 10.1007/s10495-006-0044-6.
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